Glomerulosclerosis is induced by irreversible progress of various glomerular diseases of different etiologies and histopathological pictures. It is mainly pathologically characterized by mesangial cell proliferation or increased mesangial matrix accompanied by atrophy, degeneration or collapse of glomerular cells. Examples of the etiologies of glomerulosclerosis include IgA nephropathy or diabetic nephropathy, which were reported to be characterized by mesangial cell proliferation or increased mesangial matrix. In order to establish a therapy for glomerulosclerosis, it seems important to clarify the mechanism of the onset or to understand the pathology. Thus, efforts have been made to develop experimental nephritis models that experimentally induce lesions with mesangial cell proliferation and mesangial matrix production, and a rat model of anti-Thy 1 antibody-induced nephritis was prepared (Bagchus, W. M. et al., Lab. Invest, Vol. 55, No. 6, pp. 680-687, 1986). This model shows glomerular nephritis with mesangial cell proliferation and mesangial matrix production caused by the reaction between Thy 1 antigen existing as a membrane protein in mesangial cells and an antibody against it, and drug efficacy tests in this model were reported (Masashi Haraguchi et al., Kidney International, Vol. 51 (1997), pp. 1838-1846).
Drugs such as antitumor agents or immunosuppressive agents based on activated vitamins D3 (i.e., 1,25-dihydroxyvitamins D3) have been developed since they were reported to have not only a calcemic action but also a differentiation-inducing effect (Abe E. et al., Proc. Natl. Acad. Sci. USA, Vol. 78, No. 8, pp. 4990-4994, 1981). 1,25-Dihydroxyvitamins D3 were also reported to have an antiproliferative effect on human mesangial cells (Weinreich T. et al., American Journal of Kidney Diseases, Vol. XVIII, No. 3, 1991, pp. 359-366). However, it was difficult to use 1,25-dihydroxyvitamins D3 for antiproliferative purposes due to hypercalcemia.
Thus, vitamin D3 derivatives with a low calcemic action were researched and some derivatives were developed. One of such vitamin D3 derivatives is 22-oxa-1α,25-dihydroxyvitamin D3, which was reported to show a differentiation-inducing effect without causing hypercalcemia (Abe J. et al., FEBS Lett., Vol. 226, No. 1, pp. 58-62, 1987). Japanese Patent No. 2854600 describes that 22-oxa-1α,25-dihydroxyvitamin D3 inhibits urinary protein excretion so that it is useful as a therapeutic agent for glomerulonephritis.
However, nothing has been shown about the effect of 22-oxa-1α,25-dihydroxyvitamin D3 on mesangial cell proliferation or mesangial matrix production.